1. Field of the Invention
Interleukin-1 (IL-1) is the name for a family of molecules which have multiple biological effects. The name interleukin-1 was proposed in 1979; and earlier literature reports refer to it by some other name. Murphy, British Journal of Rheumatology, 1985; 24(suppl 1): 6-9, and Oppenheim et al., Immunology Today, vol. 2, 45-55(1986). IL-1 is secreted by stimulated macrophages, and has several significant biological effects, such as mediation of T-lymphocyte proliferation and pyrogenic and proinflammatory effects.
IL-1 activities are summarized in the two above papers. IL-1 has been described to mediate the acute phase response in inflammation, and to have pyrogenic and proinflammatory effects. IL-1 induces connective tissue changes, and has been demonstrated to induce the release of degradative enzymes from mesenchymal cells that are present at sites of bony erosion in inflammatory disease states, such as rheumatoid arthritis. Billingham, Brit. J. Rheumatology, 1985: 24(suppl 1): 25-28. Dayer, Brit. J. Rheumatology, 1985: 24(suppl 1): 15-20. The production of acute phase proteins in the hepatocytes during the acute phase of inflammation is mediated by IL-1. Whicher, Brit. J. Rheumatology, 1985: 24(suppl 1): 21-24.
IL-1 is also involved as a mediator in the inflammatory skin disease, psoriasis. Camp et al., J. Immunology 1986: 137: 3469-3474, and Ristow, Proc. Natl. Acad. Sci. USA 1987: 84: 1940-1944. It is cytotoxic for insulin producing beta cells in the pancreas, and is thus a causative factor in the development of diabetes mellitus. Bendtzen et al., Science 1986: 232: 1545-1547 and Marx, Science 1988: 239: 257-258. IL-1 also appears to be involved in the development of athersoclerotic lesions or athersclerotic plaque. Marx, Science 1988: 239: 257-258. In the absence or suppression of endogenous prostaglandins, IL-1 stimulates growth and proliferation of vascular smooth muscle cells, which could lead to thickening of vascular walls, such as occurs in atherogenesis. Libby et al., Fed. Proc. Mar. 1, 1987: Vol. 46, no. 3: 975, Abstract 3837.
It would be advantageous to control the release of IL-1, and to be able to treat IL-1-mediated effects. It would also be advantageous to control or treat IL-1 mediated inflammations, without production of concomitant side effects known to accompany the use of antiinflammatory steroids and non-steroidal antiinflammatory agents.